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The neurokinin-1 receptor antagonist aprepitant ameliorates oxidized LDL-induced endothelial dysfunction via KLF2
- Source :
- Molecular Immunology. 106:29-35
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Atherosclerosis is the main cause of many cardiovascular diseases. Endothelial dysfunction is recognized as an early event in the development of atherosclerosis. Many drugs have been studied to mitigate hyperlipidemia-induced endothelial injury. Studies have demonstrated that neuropeptide substance P (SP) and its preferred receptor neurokinin receptor 1 (NK-1R) are involved in the pathological progression of cardiovascular disease. In this study, we show that aprepitant, a selective NK-1R antagonist, possesses beneficial effects that protect endothelial cells from oxidized low-density lipoprotein (ox-LDL)-induced inflammatory response and injury. Our data demonstrate that NK-1R is expressed in both aortic and vein-originated endothelial cells and that ox-LDL treatment induces NK-1R expression. Treatment with aprepitant suppresses induction of endothelial vascular adhesion molecule (VCAM-1 and E-selectin) and cytokine by ox-LDL. The presence of aprepitant mitigates adhesion of monocytes to endothelial cells and the reduction in eNOS/NO triggered by ox-LDL. Mechanistically, we demonstrate that aprepitant suppresses ERK5-KLF2 axis activation. Silencing of KLF2 abolishes the inhibitory role of aprepitant on ox-LDL-induced inflammatory response, suggesting that its action is dependent on KLF2. Collectively, our data support that aprepitant exerts an anti-inflammatory effect. Further research is required to investigate the therapeutic potential of aprepitant in vascular inflammation resulting from atherosclerosis.
- Subjects :
- 0301 basic medicine
medicine.medical_treatment
Immunology
Kruppel-Like Transcription Factors
Vascular Cell Adhesion Molecule-1
Substance P
Pharmacology
Monocytes
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Enos
Tachykinin receptor 1
Cell Adhesion
Human Umbilical Vein Endothelial Cells
medicine
Humans
Endothelial dysfunction
Receptor
Molecular Biology
Aprepitant
Inflammation
biology
U937 Cells
Receptors, Neurokinin-1
medicine.disease
biology.organism_classification
Lipoproteins, LDL
030104 developmental biology
Cytokine
chemistry
KLF2
E-Selectin
030215 immunology
medicine.drug
Subjects
Details
- ISSN :
- 01615890
- Volume :
- 106
- Database :
- OpenAIRE
- Journal :
- Molecular Immunology
- Accession number :
- edsair.doi.dedup.....2bec9d6563289cc5d6602e6842f1a322